For biological specimens, the effective utilization of the great resolving power of the electron microscope (EM) is prevented in commercial instruments by rapidly-occurring structural changes resulting from interactions of the specimen, the residual gases, and the beam. Therefore, our first objective in the quest for the highest possible resolution has been the development of instruments in which this damage is minimized. We now have two unique instruments: (1) a JEM-6C converted to operate at 5x10 to the minus 85h power Torr with precise control of the pressure and composition of gases at the specimen, and (2) the custom-built Hitachi HV-1 operating at 2x10 to the minus 8th power Torr. For the latter a video system which utilizes silicon diode array as transducer has been designed and constructed. This system digitized data on magnetic tape in a form satisfactory for subsequent image processing the IBM 360/44 computer of the Image Processing Laboratory. Preliminary tests indicate that the resolution and the signal-to-noise ratio of the information stored by this system will be limited only by the information contained in the primary EM beam. The question of "beam damage" is one of the most important in the field, and one with much pessimism. However, preliminary results indicate that in these instruments conditions can be arranged to obtain remarkable stability. Our results indicate that the agent of destruction under the usual operating conditions is water vapor in "water-gas-type" reactions, and, in our opinion, one cannot study primary radiation damage unless the partial pressure of water is less than 5x10 to the minus 9th power Torr. The continuation of this program will primarily be concerned with the utilization on these two systems to obtain quantitative data concerning changes which occur in specimens while being irradiated in the electron microscope, the development of satisfactory specimens for high resolution biological EM, and the utilization of these results to obtain useful high resolution information concerning structures of biological interest.